Rapid modulation of long-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons
Rapid modulation of long-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons
复制标题
DOI：
10.1111/j.1471-4159.2006.04264.x
复制
发表时间：
2007-02-01
影响因子：
4.7
通讯作者：
Kawato, Suguru
中科院分区：
文献类型：
--
作者：
Mukai, Hideo;Tsurugizawa, Tomokazu;Kawato, Suguru
雌激素对海马突触可塑性的快速调节一直是研究的热点，但通过突触雌激素受体分析其分子机制一直是一个非常困难的问题。在这里，两种类型的独立的突触可塑性，长期抑郁症（LTD）和棘，进行了调查，在响应17 β-雌二醇和雌激素受体激动剂使用成年雄性大鼠海马切片。多电极研究表明，雌二醇迅速增强LTD不仅在CA 1，而且在CA 3和齿状回。树突棘形态学分析表明，薄型棘密度选择性增加，在CA 1锥体神经元后2小时内应用1 nM雌二醇。这种增强的棘生成被丝裂原活化蛋白（MAP）激酶抑制剂完全抑制。只有雌激素受体（ER）α激动剂，（丙基-吡唑-trinyl）三苯酚（PPT），诱导相同的增强作用，雌二醇对LTD和棘在CA 1。ER β激动剂，（4-羟基苯基）-丙腈（DPN），抑制LTD，不影响棘。由于雌二醇的突触调节模式与ER α激动剂的模式基本相同，因此使用经ER α敲除（KO）小鼠鉴定的纯化RC-19抗体对突触ER α进行了研究。用免疫金电镜和免疫组化方法证明ER α在主海马神经元棘中的定位。ER α也定位于细胞核、细胞质和突触前。
Rapid modulation of hippocampal synaptic plasticity by estrogen has long been a hot topic, but analysis of molecular mechanisms via synaptic estrogen receptors has been seriously difficult. Here, two types of independent synaptic plasticity, long-term depression (LTD) and spinogenesis, were investigated, in response to 17 beta-estradiol and agonists of estrogen receptors using hippocampal slices from adult male rats. Multi-electrode investigations demonstrated that estradiol rapidly enhanced LTD not only in CA1 but also in CA3 and dentate gyrus. Dendritic spine morphology analysis demonstrated that the density of thin type spines was selectively increased in CA1 pyramidal neurons within 2 h after application of 1 nM estradiol. This enhancement of spinogenesis was completely suppressed by mitogen-activated protein (MAP) kinase inhibitor. Only the estrogen receptor (ER) alpha agonist, (propyl-pyrazole-trinyl) tris-phenol (PPT), induced the same enhancing effect as estradiol on both LTD and spinogenesis in the CA1. The ERbeta agonist, (4-hydroxyphenyl)-propionitrile (DPN), suppressed LTD and did not affect spinogenesis. Because the mode of synaptic modulations by estradiol was mostly the same as that by the ERalpha agonist, a search was made for synaptic ERalpha using purified RC-19 antibody qualified using ERalpha knockout (KO) mice. Localization of ERalpha in spines of principal glutamatergic neurons was demonstrated using immunogold electron microscopy and immunohistochemistry. ERalpha was also located in nuclei, cytoplasm and presynapses.